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elifesciences.orgFEATURE ARTICLE
THE NATURAL HISTORY OF MODEL ORGANISMS
Peromyscus mice as a modelfor studying natural variationAbstract The deer mouse (genus Peromyscus) is the most abundant mammal in North America, and it
occupies almost every type of terrestrial habitat. It is not surprising therefore that the natural history
of Peromyscus is among the best studied of any small mammal. For decades, the deer mouse has
contributed to our understanding of population genetics, disease ecology, longevity, endocrinology
and behavior. Over a century’s worth of detailed descriptive studies of Peromyscus in the wild,
coupled with emerging genetic and genomic techniques, have now positioned these mice as model
organisms for the study of natural variation and adaptation. Recent work, combining field
observations and laboratory experiments, has lead to exciting advances in a number of fields—from
evolution and genetics, to physiology and neurobiology.
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NICOLE L BEDFORD AND HOPI E HOEKSTRA*
IntroductionPeromyscus is a genus of small North American
rodents known colloquially as deer mice (Emmons,
1840). When the first Peromyscus specimens were
shipped to European systematicists in the late 18th
century, their resemblance to the local wood
mouse prompted the designation Mus sylvaticus
(Hooper, 1968). At the time, little was known of
the diversity of rodents worldwide and most were
assigned the generic term Mus (Linnaeus, 1758).
The name Peromyscus (Gloger, 1841) was first
employed, albeit narrowly, in the middle of the
19th century. Quadrupeds of North America
(Audubon and Bachman, 1854) recognized only
three species now known to belong to Peromyscus,
and Mammals of North America (Baird, 1859)
included a mere 12. But by the turn of the 20th
century, Peromyscus included 143 forms, 42 of
which represented monotypic or good biological
species (Osgood, 1909). The genus saw several
additional revisions throughout the 20th century as
North American mammalogy matured and natural
history collections expanded. Today 56
species are recognized, the most widespread
and diverse being Peromyscus maniculatus
(Musser and Carleton, 2005).
Thus, although not immediately appreciated,
Peromyscus includes more species than any other
North American mammalian genus and, apart
from Mus and Rattus, more is known concerning
its biology in the laboratory than any other group
of small mammals (Figure 1; King, 1968;
Kirkland and Layne, 1989). Several disciplines
including ecology, evolution, physiology, repro-
ductive biology and behavioral neuroscience
have all employed Peromyscus, inspiring its label
as ‘the Drosophila of North American mammalogy’
(Dewey and Dawson, 2001). Arguably, the
emergence of Peromyscus as a model system
was propelled by our cumulative knowledge of
its fascinating and varied natural history.
Distribution and habitat‘Within the range of one species (maniculatus) it
is probable that a line, or several lines, could be
drawn from Labrador to Alaska and thence to
southern Mexico throughout which not a single
square mile is not inhabited by some form of this
species’ (Osgood, 1909).
Wilfred H Osgood asserted that some form of
Peromyscus had been trapped in nearly every
patch of North America ever visited by a mammal
collector. Members of the genus are distributed
from the southern edge of the Canadian Arctic to
the Colombian border of Panama (Figure 2).
Various demographic and biogeographic factors
(e.g., Pleistocene glacial and pluvial cycles, pop-
ulation expansions, mountain range elevations
*For correspondence:
Copyright Bedford and Hoekstra.
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and sea-level changes) have influenced the
diversity and distribution of deer mice (Sullivan
et al., 1997; Riddle et al., 2000; Dragoo et al.,
2006; Kalkvik et al., 2012; Lopez-Gonzalez
et al., 2014). The result is a mosaic of widespread
and restricted species ranges shaped by both
dispersal and vicariance events. Our knowledge
of the distributions, home ranges and habitat
preferences of deer mice comes primarily from
the trapping data and field notes of early natural
historians (e.g., Sumner, 1917; Dice, 1931;
Blair, 1940, 1951). Osgood’s influential 1909
taxonomic revision was built on examinations of
more than 27,000 specimens from diverse
locales that were collected primarily by the US
Biological Survey. Today, more than 120,000
Peromyscus specimens are accessioned in
Natural History museums across North America
and the United Kingdom (Table 1). These invalu-
able collections document more than a century of
dynamic relationships between deer mice and
their environment. For example, by comparing
past and present-day collecting locales, shifts in
the distributions of deer mice have been linked to
climate change (Moritz et al., 2008; Yang et al.,
2011; Rowe et al., 2014), and morphological
analyses of these museum specimens reveal how
deer mice respond to changing environments
(Grieco and Rizk, 2010).
Although not strictly commensal, deer mice
(particularly in New England) do enter human
households and partake of their larders.
According to legend, Walt Disney drew inspiration
for Mickey Mouse from the ‘tame field mice’
(most likely Peromyscus leucopus) that would
wander into his old Kansas City animation studio
(Updike, 1991). Nevertheless, Peromyscus are
most commonly trapped in woodlands and
brushlands and are also found in tropical and
temperate rainforests, grasslands, savannas,
swamps, deserts and alpine habitats (Figure 3;
Baker, 1968). Local adaptation to these various
environments has been the subject of much
recent inquiry (e.g., Linnen et al., 2013;
Natarajan et al., 2013; MacManes and Eisen,
2014), and the detailed cataloguing of pheno-
typic diversity by early naturalists inspired much
of this work. However, we still require a more
complete understanding of ecological diversity
across the entire genus, as well as an enlightened
view of phylogenetic relationships informed by
whole-genome sequences (see Box 1).
Adaptation to mountains, citiesand desertsAmong North American mammals, the deer mouse
is unparalleled in its ability to colonize an impressive
array of habitats. The remarkable elevational range
Figure 1. Simplified phylogeny depicting the relationships among muroid rodent model organisms. Peromyscus
belong to the Cricetidae family, which includes voles (Microtus), hamsters (Mesocricetus), and New World rats and
mice. Old World rats and mice belong to the Muridae family, which include the familiar laboratory rat (Rattus
norvegicus) and mouse (Mus musculus). Muridae and Cricetidae diverged roughly 25 million years ago. Schematic
based on based on phylogeny data from Steppan et al. (2004). Image credit, Nicole Bedford and Hopi Hoekstra.
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Feature article The natural history of model organisms | Peromyscus mice as a model for studying natural variation
of one subspecies (P. m. sonoriensis) stretches from
below sea level in Death Valley to above 4300
meters in the adjacent White and Sierra Nevada
mountain ranges (Hock, 1964). The ability of
deer mice to colonize and thrive in low-oxygen
environments is due, in part, to standing genetic
variation in globin genes (Snyder, 1981; Natar-
ajan et al., 2015). Storz and colleagues (2007,
2009) pinpointed several amino acid substitutions
that confer high hemoglobin-O2 affinity and
better aerobic performance at high altitudes.
Functional analyses have since identified how
Figure 2. North American distributions of eight Peromyscus species currently maintained as outbred laboratory
stocks (based on data from Hall, 1981). Some ranges are narrow and others are extensive, with many overlapping to
a large extent. Simplified tree indicating phylogenetic relationships among taxa is shown; branch lengths are
arbitrary (based on data from Bradley et al., 2007). The most widespread and ecologically diverse group is also the
best represented in the laboratory: six P. maniculatus subspecies are maintained in laboratories across the United
States. Collecting localities of colony founders are indicated by numbered squares (see also Table 2). Image credit,
Nicole Bedford and Hopi Hoekstra.
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Table 1. Museums with the largest collections of Peromyscus specimens
Collection Location No. specimens
Smithsonian National Museum ofNatural History
Washington, DC 38,406
Museum of Vertebrate Zoology Berkeley, CA 34,131
American Museum of Natural History New York, NY 19,234
Field Museum Chicago, IL 8939
Museum of Comparative Zoology Cambridge, MA 7754
Canadian Museum of Nature Ottawa, ON 6315
Academy of Natural Science Philadelphia, PA 2425
Natural History Museum London, UK 2238
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Feature article The natural history of model organisms | Peromyscus mice as a model for studying natural variation
precise mutations, and interactions among muta-
tions, affect hemoglobin-O2 affinity, demonstrat-
ing that the adaptive value of a given biochemical
substitution depends both on the local environ-
ment and the genetic background in which it
arises (Natarajan et al., 2013).
The process of adapting to urban environ-
ments also leaves its mark on the genome
(Pergams and Lacy, 2008; Munshi-South and
Kharchenko, 2010; Munshi-South and Nagy,
2014). By comparing the brain, liver and gonad
transcriptomes of urban and rural populations of
P. leucopus, Harris et al. (2013) identified
several genes associated with metabolism and
immune function exhibiting signatures of selec-
tion in New York City’s parklands. Similarly,
MacManes and Eisen (2014) identified renal
transcripts related to solute and water balance
experiencing purifying selection in the desert-
adapted species, Peromyscus eremicus. Further
study of these candidate genes will determine
their role in adaptation to new or extreme
environments.
Diet and predatorsGenerally deer mice are granivores, feeding
primarily on seeds, but fruits, fungi, green
vegetation and insects have been found among
their stomach contents and in the nest cavities of
their burrows (Gentry and Smith, 1968; Wolff,
1985). However, some species have evolved
seasonally specialized diets. In the winter, Per-
omyscus melanotis prey almost exclusively on
monarch butterflies that roost in Mexico’s central
highlands (Brower et al., 1985). Moreover, on
a remote island in British Columbia, Peromyscus
keeni feast on auklet eggs during the seabird
breeding season (Drever et al., 2000). Deer mice
are themselves common prey, contributing to the
diets of many predators such as weasels, skunks,
lynx, bobcats, foxes, coyotes, hawks and owls
(Luttich et al., 1970; Bowen, 1981;Montgomery,
1989; Van Zant andWooten, 2003). Indeed, avian
predation imposes strong selective pressure for
cryptic coloration in Peromyscus—a classic exam-
ple of local adaptation (Vignieri et al., 2010;
Linnen et al., 2013).
Parasites and diseaseThe diversity of parasites is documented for only
a few Peromyscus species, and very little is known
of the ecological factors that influence infection
dynamics. Common internal parasites include
pentastomid larvae, cestode tapeworms, nemat-
odes and trematodes (Whitaker, 1968; Pedersen
and Antonovics, 2013). External parasites include
Figure 3. The ecology of Peromyscus varies considerably both within and among species. (A) The forest-dwelling
deer mouse, P. maniculatus nubiterrae, perches high on a tree branch in Southwestern Pennsylvania. (B) The beach
mouse, P. polionotus phasma, takes shelter among the dune grasses on Florida’s Atlantic coast. (C) Its mainland
counterpart, the oldfield mouse, P. polionotus sumneri, is typically found in fallow fields and is sympatric with the
cotton mouse, P. gossypinus (D), which occupies adjacent stands of long leaf pine. Image credits: A, Evan P
Kingsley; B, JB Miller; C, D, Nicole Bedford.
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Feature article The natural history of model organisms | Peromyscus mice as a model for studying natural variation
lice, mites, fleas and ticks (Whitaker, 1968), the
latter two being vectors of plague and Lyme
disease, respectively (Allred, 1952; Burgdorfer
et al., 1982; Gage and Kosoy, 2005).
As a natural reservoir for Borrelia burgdorferi—the
bacterial agent of Lyme disease—Peromyscus is
the subject of much research on the pathogenesis
and transmission of the disease (Bunikis et al.,
2004; Ramamoorthi et al., 2005; Schwanz et al.,
2011; Baum et al., 2012). Peromyscus also fea-
tures in ecological modeling efforts to determine
how the diversity of the tick host community
impacts disease risk (LoGiudice et al., 2003,
2008). One hypothesis for the alarming recent
expansion of Lyme disease is that habitat frag-
mentation associated with human development
favors deer mouse populations at the expense of
other tick hosts (e.g., squirrels and shrews) that are
poor reservoirs for the disease (LoGiudice et al.,
2003; Schwanz et al., 2011). Peromyscus is also
a notorious carrier of the Sin Nombre hantavirus,
responsible for the deaths of 12 people in the
Four Corners area of the southwestern United
States in 1993.
LongevityMortality in natural populations is incredibly high
and driven by a combination of factors including
limited food supply, competition for territories
and predation (Bendell, 1959). As such, most
Peromyscus are thought to live less than a year
in the wild (Terman, 1968). However, early
investigators noted substantially longer natural
lifespans in their laboratory colonies (Sumner,
1922; Dice, 1933). With a twofold difference in
life expectancy, Sacher and Hart (1978) pro-
posed P. leucopus and Mus musculus as a lon-
gevity contrast pair. P. leucopus—which lives up
to 8 years and may remain fertile for 5—produces
fewer reactive oxygen species, exhibits enhanced
antioxidant enzyme activity and less oxidative
damage to lipids relative to the short-lived (~3.5years) laboratory mouse (Sohal et al., 1993;
Shi et al., 2013). Measuring the biochemical
correlates of longevity in Peromyscus has been
integral to providing support for the oxidative
stress theory of aging (Ungvari et al., 2008).
Life historyThe timing of life history events in Peromy-
scus—well documented from field and laboratory
studies alike—is highly variable both within and
among species. Yet studies contrasting the
reproductive and developmental patterns of wild
and domesticated deer mice have found few
significant differences (Millar, 1989; Botten
et al., 2000). Here, we highlight life history traits
in P. maniculatus, the most commonly used
laboratory species. Gestation ranges from 21 to
27 days (average 23.6) and average litter size is
4.6 pups (Millar, 1989). Juveniles first leave the
nest between 14 and 16 days of age (Vestal
et al., 1980) and become independent of their
mother between 18 and 25 days (Millar, 1989).
Box 1. Priorities for Peromyscusresearch
Discovering as yet untapped ecological diversity
Much of our understanding of Peromyscus biology comes
from studies of two ubiquitous species that have proven
amenable to laboratory life—P. maniculatus and P.
leucopus. However, most Peromyscus species remain
comparatively understudied, particularly in Central Amer-
ica and Mexico where taxonomic diversity and endemism
(i.e., where species are unique to a given geographic
location) is greatest.
Sequencing more Peromyscus genomes and revising
their phylogeny
A comprehensive phylogeny based on genome-wide
DNA sequences would greatly facilitate the comparative
approaches that are the unique advantage of the
Peromyscus system. An annotated genome assembly is
currently available for P. maniculatus bairdii (Pman_1.0,
GenBank assembly accession GCA_000500345.1) and
draft sequences are available for P. californicus, P.
leucopus and P. polionotus (Baylor College of Medicine,
www.hgsc.bcm.edu/peromyscus-genome-project). Sev-
eral more Peromyscus genomes are being sequenced, but
still more are needed.
Identifying where Peromyscus can complement bio-
medical studies of other laboratory species
The genetically diverse Peromyscus could be used more
widely in biomedical research than previously thought.
Indeed, certain aspects of human biology—including
aging, epigenetics, retinal development and hematolo-
gy—have been suitably modeled in Peromyscus (e.g.,
Ungvari et al., 2008; Shorter et al., 2012; Arbogast
et al., 2013; Sun et al., 2014).
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Feature article The natural history of model organisms | Peromyscus mice as a model for studying natural variation
Captive females give birth to their first litter, on
average, at 84 days (Haigh, 1983), but males are
capable of siring offspring several weeks earlier.
The actual timing of sexual maturation in the
wild, however, is often dictated by population
density, food availability and season. In response
to short day length, many species exhibit
seasonal gonadal regression (Trainor et al.,
2006), increased aggression (Trainor et al.,
2007), impaired spatial memory (Workman
et al., 2009) and enhanced immune function
(Prendergast and Nelson, 2001). As such,
Peromyscus has emerged as a model system for
the study of photoperiodism (i.e., the ability to
seasonally modulate energetic demands by
tracking day length changes). Such studies have
been particularly fruitful for understanding the
mechanistic basis of gene by environment inter-
actions. For example, day length can reverse the
behavioral action of the hormone estradiol by
determining which estrogen receptor pathway is
expressed and consequently activated (Trainor
et al., 2007). While life history traits are strongly
affected by environmental cues, substantial ge-
netic variation in the neuroendocrine pathways
that control reproductive timing also exists, as
demonstrated by selection line experiments with
photoperiod responsive and nonresponsive
P. leucopus (Heideman et al., 1999; Heideman
and Pittman, 2009).
Mating system and parental careWhile the majority of Peromyscus species are
promiscuous, monogamy has independently
evolved at least twice in the genus (Turner
et al., 2010). Both Peromyscus californicus
(Gubernick and Alberts, 1987; Ribble, 1991)
and Peromyscus polionotus (Smith, 1966;
Foltz, 1981) are socially and genetically monog-
amous, and both males and females contribute to
the care of offspring. P. californicus, in particular,
has become an important neurobiological model
for the study of male parental care (Bester-
Meredith et al., 1999; Trainor et al., 2003; Lee
and Brown, 2007; de Jong et al., 2009, 2010).
As a complement, the ability of monogamous
P. polionotus to hybridize with promiscuous
P. maniculatus allows geneticists to identify the
genetic basis of alternate mating systems and
their associated phenotypes, from genomic
imprinting (Vrana et al., 2000) to parental
investment and reproductive traits (e.g., Fisher
and Hoekstra, 2010).
Rosenfeld (2015) argues that parental and
social behaviors are particularly vulnerable to
endocrine disruption, as these traits are de-
pendent upon the organizational and activational
effects of androgens and estrogens. Mating
system variation between closely related species
of deer mice provides an opportunity to test this
hypothesis. P. maniculatus males exposed to the
endocrine disrupting compound bisphenol A
(BPA) during development displayed reduced
Video 1. Innate burrowing behavior in Peromyscus
can be directly observed in a laboratory setting. Here,
P. polionotus is busy constructing the long entrance
tunnel of its complex burrow. Video credit, Nicole
Bedford and Hopi Hoekstra.
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Figure 4. Genetic crosses between the pale beach
mouse P. polionotus leucocephalus (top row left) and
the darker mainland mouse P. p. polionotus (top row
right) result in first-generation F1 hybrids, all with
intermediate coloration (second row). Intercrosses
between F1 hybrids produce a variable F2 generation,
showing a continuous distribution of pigmentation
phenotypes ranging from light to dark (third and
fourth rows; Steiner et al., 2007). This segregation
pattern—initially described by Francis Sumner—is
among the earliest empirical evidence that several
discrete loci may collectively contribute to a quantitative
trait (Dobzhansky, 1937; see also Box 1). Image credit,
Nicole Bedford and Hopi Hoekstra.
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Feature article The natural history of model organisms | Peromyscus mice as a model for studying natural variation
spatial learning and exploratory behavior—traits
known to be associated with male–male compe-
tition for mates (Galea et al., 1996; Jasarevic
et al., 2011). However, these behaviors—which
are not subject to sexual selection in fema-
les—were unaffected in BPA-exposed females.
By contrast, sexual selection favors the evolution
of mate guarding and territorial behavior in
monogamous males, and it is these traits (rather
than spatial learning or exploratory behavior) that
are compromised by endocrine disruption in
P. californicus (Williams et al., 2013).
Home buildingBehavioral genetics studies have historically been
restricted to a handful of genetic model organ-
isms that display behaviors of unclear ecological
relevance (Fitzpatrick et al., 2005). Sufficient
resources are now available—from a medium-
density genetic linkage map (Kenney-Hunt et al.,
2014) to draft genome sequences (Baylor
College of Medicine, Peromyscus Genome Proj-
ect)—that we can attribute natural variation in
Peromyscus behavior to specific genetic variants.
For instance, P. maniculatus and P. polionotus
display considerable differences in stereotyped
burrowing behavior. P. maniculatus digs short,
simple burrows in contrast to the long, complex
burrows constructed by P. polionotus that consist
of an entrance tunnel, nest chamber and escape
tunnel (Dawson et al., 1988; Weber et al.,
2013). Remarkably, mice raised in the laboratory
for several generations recapitulate the species-
specific burrow architectures observed in nature
(Video 1). Furthermore, the complex burrows of
P. polionotus are derived (Weber and Hoekstra,
2009) and likely evolved through changes at only
a handful of genetic loci, each affecting distinct
behavioral modules (i.e., entrance tunnel length
and escape tunnel presence; Weber et al.,
2013). Next steps include isolating genetic
variants, understanding their effects on the
neural circuitry underlying burrowing behavior
and quantifying the adaptive value of burrowing
in the wild.
PigmentationAmong the several cases of adaptive phenotypic
variation in Peromyscus, perhaps the most
obvious is coat coloration. Recent advances
Box 2. Peromyscus and the historyof evolutionary thought
The work of early Peromyscus biologists (particularly
Francis B Sumner) informed influential thinkers in pop-
ulation genetics and evolutionary biology, such as Sewall
Wright, Theodosius Dobzhansky and JBS Haldane. Since
most early 20th century geneticists came from experi-
mentalist backgrounds, many turned to naturalists for data
from wild populations (Provine, 1986). At the time,
Sumner’s work on geographic variation in Peromyscus
represented one of the few major studies of evolution in
natural populations. As such, Wright closely followed
Sumner’s analysis of phenotypic intergradation between
geographically contiguous P. maniculatus subspecies in
California (Sumner, 1918). Wright concluded that the
observed quantitative differences in coat color were
determined by the accumulation of several discrete (i.e.,
Mendelian) factors (Wright, 1932). The question of
whether continuous (or quantitative) traits are subject to
the same rules of inheritance as discrete characters was
central to the Modern Evolutionary Synthesis.
Between 1914 and 1930, Sumner carefully measured
several quantitative traits—most notably coat color—that
varied among geographically distinct subspecies of
Peromyscus, which he then crossed in the laboratory
(Figure 4; Sumner, 1930). Dobzhansky (1937) high-
lighted these data as empirical support for the multiple
gene hypothesis for the inheritance of quantitative traits.
Later, Haldane (1948) applied a theoretical model to the
gradient of increasing pigmentation observed in P.
polionotus populations from coastal to inland Florida
(Sumner, 1929). From these data, he estimated the local
strength of selection acting on a putative pigmentation
locus in the wild—the dominant white-cheek character
(Wc) identified by Blair (1944).
Peromyscus also featured in Dobzhansky’s studies of
reproductive isolation. Certain P. maniculatus subspecies
with overlapping geographic distributions are neverthe-
less separated by habitat, often with one subspecies
inhabiting prairie, open fields or sandy lake beaches, and
the other being exclusively forest-dwelling (Dice, 1931).
These sub-specific forms readily produce viable and fertile
offspring in the laboratory yet remain reproductively
isolated in the wild—a prime example of ecological
isolation (Dobzhansky, 1937). Peromyscus has thus been
a cornerstone of evolutionary biology for nearly a century.
These and other studies drew the attention of biologists in
many fields, launching the many, varied Peromyscus
research programs we see today.
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Feature article The natural history of model organisms | Peromyscus mice as a model for studying natural variation
have identified not only the genes, but also
the specific mutations, leading to local variation
in coat color. Beach mice (P. polionotus leuco-
cephalus) living on the coastal sand dunes and
barrier islands of Florida are considerably
paler than their inland counterparts (P. p.
subgriseus) that inhabit dark, loamy soils
(Figure 4; Howell, 1920; Sumner, 1929). For
beach mice on Florida’s Gulf Coast, light
coloration is due, in part, to a fixed single
nucleotide polymorphism (SNP) in the
melanocortin-1 receptor (Mc1r) coding region
(Hoekstra et al., 2006). However, this Mc1r
allele does not contribute to light pelage in
Florida’s Atlantic coast mice, suggesting that
the two populations converged on light color-
ation independently (Steiner et al., 2007).
Similarly, backgroundmatching in P. maniculatus
of the Nebraska Sand Hills affords a strong
selective advantage against avian predators
(Linnen et al., 2013). Yet, cryptic coloration is
a complex phenotype composed of multiple
component traits (i.e., tail stripe, dorsal-
ventral boundary, ventral color, dorsal bright-
ness and hue). Linnen and colleagues (2013)
identified multiple distinct mutations within
the Agouti locus, each associated with a differ-
ent color trait that independently affected
fitness. Thus, parallel studies of Peromyscus
pigmentation nicely illustrate the marriage
between classical natural history studies and
modern molecular techniques, thereby pro-
viding new insights into the molecular basis
of adaptation.
Peromyscus in the laboratoryFrancis Sumner, considered the grandfather of
Peromyscus biology (see Box 2), first demon-
strated the feasibility of the deer mouse as
a laboratory organism in the 1910s and 20s. He
famously built the first Peromyscus ‘mouse
house’ in what is now referred to as Sumner
Canyon at the Scripps Institution in La Jolla,
California. When his Peromyscus work at Scripps
was discontinued, Sumner bequeathed his stocks
to Lee R Dice at the University of Michigan who
honed the methods for generating and maintain-
ing Peromyscus colonies in the 1930s and 40s.
During this time, Dice began to catalogue single
factor genetic mutations in his stocks (e.g., gray,
dilute, epilepsy). These mice served as the
founding strains for the Peromyscus Genetic
Stock Center (PGSC) established in 1985 by
Wallace Dawson at the University of South
Carolina, which currently maintains wild-derived
stocks of six species, as well as 13 coat-color
mutants and four additional mutants on
P. maniculatus genetic backgrounds. Additional
wild-derived stocks are kept in individual labora-
tories (Table 2) and still more mutants have been
cryopreserved. The PGSC also maintains an
Table 2. Current laboratory colonies of Peromyscus
Species Year Source population Location
1 P. californicus insignis 1979–1987 Santa Monica Mts., CA PGSC
2 P. eremicus sp. 1993 Tucson, AZ PGSC
3 P. polionotus subgriseus 1952 Ocala National Forest, FL PGSC
4a P. maniculatus bairdii 1946–1948 Ann Arbor, MI PGSC
4b P. m. sonoriensis 1995 White Mtn. Research Station, CA PGSC
4c P. m. rufinus 1998 Manzano Mtn., NM UNM
4d P. m. nubiterrae 2010 Powder Mill Nature Reserve, PA HU
4e P. m. rufinus 2014 Mt. Evans, CO UIUC
4f P. m. nebrascensis 2014 Lincoln, NE UIUC
5 P. leucopus sp. 1982–1985 Linville, NC PGSC
6 P. gossypinus gossypinus 2009 Jackson County, FL HU
7 P. melanophrys xenerus 1970–1978 Zacatecas, Mexico UIUC
8 P. aztecus hylocetes 1986 Sierra Chincua, Mexico UIUC
The year and population from which the founders were collected are noted. Numbers refer to collecting localities
shown in Figure 2. PGSC: Peromyscus Genetic Stock Center; UNM: University of New Mexico; HU: Harvard
University; UIUC: University of Illinois at Urbana-Champaign.
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extensive online reference library (http://stkctr.
biol.sc.edu) with more than 3000 citations.
While the genetic causes and phenotypic
consequences differ among strains, Peromyscus
colonies are invariably susceptible to inbreeding
depression, which necessitates their maintenance
as relatively outbred stocks (Lacy et al., 1996;
Joyner et al., 1998). Thus, although the deer
mouse is amenable to laboratory life, its
biology has not been purposely altered by
generations of inbreeding or artificial selec-
tion. Life history traits and even behaviors such
as burrow construction or ultrasonic vocaliza-
tion are generally preserved in laboratory
strains (Dawson et al., 1988; Millar, 1989;
Kalcounis-Rueppell et al., 2010). Thus, the
traits we scrutinize in the laboratory (e.g.,
aerobic performance, photoperiodism, mating
and parental behavior) are arguably faithful
representations of phenotypes in nature. The
ability to study genetically diverse, wild-
derived mice under controlled laboratory con-
ditions has opened up several constructive
research programs centered on understanding
the phenotypic consequences of natural
genetic variation.
ConclusionsThe tradition of dissecting the genetic basis of
ecologically relevant traits in the laboratory
began in the early 20th century; in Peromy-
scus, this effort was lead by Francis Sumner
and continues today. In an era of high-
throughput sequencing and expanding trans-
genic technologies, our concept of the genetic
model organism is rapidly changing. We can
now widen our focus to include the diverse and
naturally evolving species that may further our
understanding of life outside the laboratory.
The emergence of Peromyscus as a model
system has been largely driven by the wealth
of natural history information available for the
genus. Indeed, deer mice form the foundation
of much of our understanding of the biology of
small mammals. The multitude of ecological
conditions to which deer mice have adapted
has contributed to an impressive array of
biological diversity within a single, ubiquitous
genus. While this radiation is fascinating in its
own right, Peromyscus is arguably foremost
among nascent model systems that may aptly
model the genetic complexity of the human
condition, which too has long been shaped by
natural selection in the wild. We hope that the
continued development—primarily through
the growth of genetic and genomic resources—of
this model system will galvanize research in all
corners of biology.
Funding
Funder Grantreference Author
Howard HughesMedical Institute
Hopi EHoekstra
Natural Sciences andEngineering ResearchCouncil of Canada(Conseil de Recherchesen Sciences Naturelleset en Genie du Canada)
421595-2012 Nicole LBedford
The funders had no role in study design, data collectionand interpretation, or the decision to submit the workfor publication.
Author contributions
NLB, HEH, conceived and wrote the paper
Nicole L Bedford Department of Organismic and
Evolutionary Biology, Harvard University, Cambridge,
United States; Department of Molecular and Cellular
Biology, Harvard University, Cambridge, United States;
Museum of Comparative Zoology, Harvard University,
Cambridge, United States and Howard Hughes Medical
Institute, Harvard University, Cambridge, United States
http://orcid.org/0000-0001-5700-1774
Hopi E Hoekstra Department of Organismic and
Evolutionary Biology, Harvard University, Cambridge,
United States; Department of Molecular and Cellular
Biology, Harvard University, Cambridge, United States;
Museum of Comparative Zoology, Harvard University,
Cambridge, United States and Howard Hughes Medical
Institute, Harvard University, Cambridge, United States
Competing interests: The authors declare that no
competing interests exist.
Received 04 February 2015
Accepted 28 May 2015
Published 17 June 2015
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